Small nucleic acid therapeutics: delivery breakthroughs, clinical translation, and future paradigms in precision medicine.

More transparency for clinical trial data: The decision by the European Medicines Agency to make clinical trial reports publicly available could provide a boon for biomedical research.

ObjectivesUS FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on Food and...

1575 Background: Novel therapies are transforming cancer care. Regulatory review and approval are essential to deliver safe and efficacious innovations to patients. Studies prior to 2010 describe quicker approval decisions for new oncology drug registrations with the FDA compared to the EMA (median delay 238 days). Both regulatory agencies have subsequently improved procedures to expedite approval times. We compared regulatory market authorisation dates at the FDA and EMA for new oncology therapies from 2010-2020. Methods: New oncology therapeutic approvals between 2010-2020 were identified from the FDA and EMA regulatory databases. We analysed only initial approvals (not supplementary licenses) for active anti-cancer therapies (excluding biosimilars and supportive drugs). The delay in regulatory approval between the FDA and EMA was calculated in calendar days. We further analysed therapies by therapeutic class, evaluating for significant differences. Results: We identified 108 new therapy registrations during the study period. 104 (96.3%) therapies were approved by the FDA and 90 (83.3%) had EMA market authorisation. 4 (3.7%) drugs were not FDA registered, including 3 unsuccessful applications and 1 which sought licensing in a different indication. 18 (16.5%) drugs were not EMA registered, including 9 (8.8%) which did not pursue EMA licensing, 3 (2.9%) withdrawn licensing applications, 3 (2.9%) sought licensing in different tumour group/indication, 1 (0.9%) rejected application and 2 (1.9%) with applications under review at submission date. Of the 86 drugs approved by both agencies, 80 were approved first by the FDA and 6 by the EMA. The median delay in approval between the FDA and EMA was 227 days (IQR:124-354 days). Table shows approvals by therapeutic class. The shortest median time difference for approval was for monoclonal antibodies (171 days) with the longest for kinase inhibitors (281 days). Conclusions: This study shows more new oncology therapies are approved by the FDA than the EMA. Patients in the US typically have access to approved therapies earlier than in Europe. From 2010 to 2020 the median delay between FDA and EMA approval was 227 days, falling by 11 days compared to 2003-10, [non-statistically significant]. Such lengthy delays could exceed the life expectancy of many patients with advanced cancer. Innovations for accelerated approval at both the FDA (e.g. Project Orbis) and EMA (e.g., PRIME) have potential to lead to faster approval.[Table: see text]

e13731 Background: Drug approval processes by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) often shape regulatory decisions globally. This study describes the particularities of drug approval of systemic therapies for sarcomas by the FDA and EMA and compares them with those of three Latin American regulatory authorities: Brazil's ANVISA, Argentina's ANMAT, and Mexico's COFEPRIS. The aim is to elucidate the similarities and differences in approval practices, which may inform future regulatory strategies in these regions. Methods: We conducted a comprehensive review of all cancer drugs approved by the FDA and EMA for the treatment of sarcoma over the past 15 years and matched to approvals in Brazil, Argentina, and Mexico. These countries were chosen due to their population size and the accessibility of their health agencies’ databases. The regulatory agencies’ websites were consulted for the registration of drugs approved between January 1st, 2009, and January 1st, 2024. We analyzed the characteristics of studies, availability of approvals based on randomized controlled trials (RCTs), overall survival (OS), and the interval between FDA and EMA approvals compared to each of the three assessed Latin American regulatory agencies. Additionally, we included drugs granted tissue-agnostic approval, recognizing the potential necessity for sarcoma treatments to be guided by biomarker-driven decisions. Results: Over the past 15 years, 19 drugs have been approved for by the FDA to treat sarcomas, and 13 by the EMA. The FDA led the approvals, granting authorization to 18 of these treatments first, with Trabectedin being the sole exception, approved earlier by the EMA and COFEPRIS. Mifamurtide is the only new drug against sarcoma licensed by the EMA but not by the FDA. During this period Argentina approved 8 of these drugs, Mexico 7, and Brazil 6. When comparing the median approval times, there was a 3.03-year interval from the FDA to the Latin American agencies (range: -6 to 5.7 years) and a 3.22-year interval from the EMA (range: -0.2 to 11.8 years). Phase 3 trial-based approvals constituted 83.3% for COFEPRIS, 75% for ANMAT, 66.7% for ANVISA, 61.5% for EMA, and 36.8% for FDA. Regarding approvals contingent on OS data, ANMAT had 37.5%, ANVISA: 33.3%, COFEPRIS 28.5%, compared to EMA 23%, and FDA 10.5%. Additionally, within this timeframe, 52.3% of FDA approvals were contingent on biomarkers, compared to 50% for EMA, 10.5% for ANVISA, and 5.2% for both ANMAT and COFEPRIS. Conclusions: The observed discrepancies in drug approval timelines and the lower number of drug approvals in Latin American countries, as compared to those by the FDA and EMA, may exacerbate disparities in treatment accessibility for sarcoma patients in these regions. Approvals of sarcoma drugs by regulatory agencies of Latin American countries were more frequently conditioned to phase 3 trials and overall survival benefit.

This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x2-tests were performed for the analysis. From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC. There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007-2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

ObjectiveTo compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014–2016.DesignUsing publicly available...

US Food and Drug Administration and European Medicines Agency Launch Good Clinical Practices Initiative

Comparison of the EMA and FDA Guidelines on Ulcerative Colitis Drug Development

BackgroundICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) have transformed outcomes in many cancer types. Prompt regulatory approval is essential to...

Introduction: the drug approval is essential to any drugs to get in the market for use by patients. The current overview have been focuses on novel drugs approvals by European medicine agency (EMA) and food and drug administration (FDA).Objective: The researchers have been focused on the different between the EMA and FDA novel drugs approval during three years. Method: Throughout extracts the data from EMA and FDA and other sources and analyze the results like orphan drugs, dosage form, number of approvals, route of administration, pharmacotherapeutic class of novel drugs in both agencies.Result: In 2020, the EMA and FDA approved 39 and 53 new drugs, respectively. In 2021, the EMA approved 54 drugs, while the FDA approved 50 drugs for 2022 EMA approved 41 drugs, while the FDA approved 37. For orphan drug designation FDA had higher orphan designation than the EMA, in term of route of administration the vast majority of FDA approved drugs were parenteral drugs.Over the last three years. On the other hand, EMA approved parenteral drugs were also the highest percent. Likewise in terms of dosage form, the solid dosage forms in both EMA and FDA had the upper hand except for 2021 in the FDA. in the pharmacotherapeutic class of the EMA and FDA show high percent of antimicrobial agents, antineoplastic agents, and endocrine agents. Conclusion: The drug approval processes of the EMA and FDA exhibit similarities and differences. This Variations highlight the distinct regulatory considerations and priorities of each agency. Understanding these factors is vital for company, healthcare providers and general knowledge

Nanomaterials for Therapeutic RNA Delivery

432 Background: The past 2 decades has witnessed a transformation in the GU cancer therapy armamentarium. In this study, we analysed GU cancer therapy approvals (initial & supplemental) by the two largest global regulators (EMA and FDA) by evaluating approval timing, labels, biomarker requirements and drug withdrawal(s). Methods: A cross-sectional analysis of approved drugs and indications made for GU cancer medicines from each regulatory database from 2003-2023 was performed. We compared new approved therapies, indications and biomarker requirements. Results: The FDA approved 40 new therapies, corresponding to 57 indications, with 2 withdrawals. The EMA approved 33 new therapies, corresponding to 43 indications with 1 withdrawal. Overall, the FDA approved new GU cancer therapies 128 days earlier (table). In renal cell carcinoma (RCC), the FDA approved 14 new therapies across 18 indications, compared to 14 new therapies across 16 indications for the EMA. The FDA approved new RCC therapies 113 days earlier than the EMA. For concomitant approvals the FDA label was broader for 5 indications, more restrictive for 2 and equivocal for 9. In urothelial cancer (UC), the FDA approved 9 new therapies across 14 indications, compared to 7 new therapies across 7 indications for the EMA. The FDA approved new UC therapies 110 days earlier than the EMA. For concomitant approvals, the FDA label was broader for 4 indications and equivocal for 3. In prostate cancer (PC), the FDA approved 17 new therapies across 25 indications, compared to 12 new therapies across 20 indications for the EMA. The FDA approved new PC therapies 157 days earlier than the EMA. For concomitant approvals, the FDA label was broader for 2 indications and equivocal for 18. Across GU cancer, 8 therapies (both FDA and EMA) had biomarker-based eligibility with 3 notable differences in urothelial cancer: the EMA uniquely requires a PD-L1 combined positive score (CPS) ≥ 10 and PD-L1 ≥ 1% for pembrolizumab (platinum-ineligible) and Nivolumab (adjuvant), respectively. Although biomarker requirement was similar, the FDA has withdrawn atezolizumab in UC unlike the EMA. Conclusions: Over the past 20 years, there has been a substantial increase in new therapies to manage GU cancers. Patients in the US typically have access to more new therapies, earlier and across broader indications than those in Europe. However, a greater number of therapies are withdrawn after approval in the US. Biomarker-eligibility is broadly similar, with some discordance in UC. [Table: see text]

PSY105 - The Rise of Orphan Drugs In Europe Vs The United States: Comparing Orphan Drug Designations Between The Ema And Fda

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) produce guidelines for the design of pivotal psychiatric drug trials used in new drug applications. It is unknown who are involved in the guideline development and what specific trial design recommendations they give. Cross-sectional study of EMA Clinical Efficacy and Safety Guidelines and FDA Guidance Documents. Study outcomes: (1) guideline committee members and declared conflicts of interest; (2) guideline development and organisation of commenting phases; (3) categorisation of stakeholders who comment on draft and final guidelines according to conflicts of interest ('industry', 'not-industry but with industry-related conflicts', 'independent', 'unclear'); and (4) trial design recommendations (trial duration, psychiatric comorbidity, 'enriched design', efficacy outcomes, comparator choice). Protocol registration https://doi.org/10.1101/2020.01.22.20018499 (27 January 2020). We included 13 EMA and five FDA guidelines covering 15 psychiatric indications. Eleven months after submission, the EMA had not processed our request regarding committee member disclosures. FDA offices draft the Guidance Documents, but the Agency is not in possession of employee conflicts of interest declarations because FDA employees generally may not hold financial interests (although some employees may hold interests up to $15,000). The EMA and FDA guideline development phases are similar; drafts and final versions are publicly announced and everybody can submit comments. Seventy stakeholders commented on ten guidelines: 38 (54%) 'industry', 18 (26%) 'not-industry but with industry-related conflicts', six (9%) 'independent' and eight (11%) 'unclear'. They submitted 1014 comments: 640 (68%) 'industry', 243 (26%) 'not-industry but with industry-related conflicts', 44 (5%) 'independent' and 20 (2%) 'unclear' (67 could not be assigned to a specific stakeholder). The recommended designs were generally for trials of short duration; with restricted trial populations; allowing previous exposure to the drug; and often recommending rating scale efficacy outcomes. EMA mainly recommended three arm designs (both placebo and active comparators), whereas FDA mainly recommended placebo-controlled designs. There were also other important differences and FDA's recommendations regarding the exclusion of psychiatric comorbidity seemed less restrictive. The EMA and FDA clinical research guidelines for psychiatric pivotal trials recommend designs that tend to have limited generalisability. Independent and non-conflicted stakeholders are underrepresented in the guideline development. It seems warranted with more active involvement of scientists and independent organisations without conflicts of interest in the guideline development process.

Policy PointsRegulatory agencies may have limited evidence on the clinical benefits and harms of new drugs when deciding whether new therapeutic agents are allowed to enter the market and under which conditions, including whether approval is granted under special regulatory pathways and obligations to address knowledge gaps through postmarketing studies are imposed.In a matched comparison of marketing applications for cancer drugs of uncertain therapeutic value reviewed by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), we found frequent discordance between the two agencies on regulatory outcomes and the use of special regulatory pathways. Both agencies often granted regular approval, even when the other agency judged there to be substantial uncertainty about drug benefits and risks that needed to be resolved through additional studies in the postmarketing period.Postmarketing studies imposed by regulators under special approval pathways to address remaining questions of efficacy and safety may not be suited to deliver timely, confirmatory evidence due to shortcomings in study design and delays, raising questions over the suitability of the FDA's Accelerated Approval and the EMA's Conditional Marketing Authorization as tools for allowing early market access for cancer drugs while maintaining rigorous regulatory standards.ContextRegulatory agencies are increasingly required to make market approval decisions for new drugs on the basis of limited clinical evidence, a situation commonly encountered in cancer. We aimed to investigate how regulators manage uncertainty in the benefit‐risk profiles of new cancer drugs by comparing decisions for the world's two largest regulatory bodies—the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA)—over a 5‐year period.MethodsWe systematically identified a set of cancer drug‐indication pairs for which data on efficacy and safety was less complete than that required for regular approval at time of market entry from 2009 to 2013, as determined by the FDA's use of Accelerated Approval (AA) or the EMA's use of Conditional Marketing Authorization (CMA) pathways, and matched these across the two agencies. Using publicly available information, we compared regulatory pathways and outcomes, final approved indications, and postmarketing obligations imposed by the agencies.FindingsWe identified 21 cancer drug‐indication pairs that received FDA AA, EMA CMA, or both. Although most applications relied on identical pivotal trials across the FDA and the EMA, regulatory pathways often differed; 57% of indications received either FDA AA or EMA CMA, and regular approval by the other agency. After approval, the EMA more often accepted single‐arm studies to confirm clinical benefit compared to the FDA (75% vs. 29% of indications), and the FDA more commonly requested randomized controlled trials (85% vs. 50%). Forty‐one percent of confirmatory trials after FDA AA were conducted in different populations than the approved indication, compared to 13% after EMA CMA. Both agencies relied primarily on surrogate measures of patient benefit for postmarketing obligations. After a median follow‐up of 7.25 years, 40% of FDA and 61% of EMA postmarketing obligations after AA and CMA, respectively, were delayed.ConclusionsUS and European regulators often deemed early and less complete evidence on benefit‐risk profiles of cancer drugs sufficient to grant regular approval, raising questions over regulatory standards for the approval of new medicines. Even when imposing confirmatory studies in the postmarketing period through special approval pathways, meaningful evidence may not materialize due to shortcomings in study design and delays in conducting required studies with due diligence.